Implantable neural electrode device separated from cerebral cortex through magnetic control telescopic contact

Abstract

The invention discloses an implantable neural electrode device separated from the cerebral cortex through magnetic control telescopic contact, and belongs to the technical field of brain signal research. Comprising a flexible substrate, a magnetostrictive deformation substrate, a magnetostrictive deformation film, an elastic component and an electrode, a plurality of rectangular grooves which are arranged in order are formed in one side of the flexible substrate; the two magnetostrictive deformation films are attached to the two sides of the magnetostrictive deformation substrate respectively, and the magnetostrictive deformation film on one side is used for fixing the magnetostrictive deformation substrate in the rectangular groove of the flexible substrate; the electrode is fixed on the magnetic deformation substrate and is used for acquiring an electroencephalogram signal; and the elastic assembly is used for pulling the deformed magnetic deformation substrate to recover to a plane state. The device is fixed under the dura mater and can be bent under the drive of a magnetic field, effective contact between the neural electrode and the cerebral cortex is achieved, and compared with a traditional semi-intrusive neural electrode, the detection quality and stability of electroencephalogram signals are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of brain signal research, and in particular relates to an implantable neural electrode device that is magnetically controlled to telescopically contact and detach from the cerebral cortex. Background Art

[0002] Brain diseases have become one of the biggest challenges facing the health field in my country and even the world. Implantable neural electrodes are key basic tools for neuroscience research. For implantable neural electrodes, the high-quality contact interface formed by the neural electrode and the neural tissue is the prerequisite for high-quality monitoring of neural electrical signals. The effective contact between the flexible electrode and the cerebral cortex helps to obtain high-quality EEG signals. However, long-term contact / friction between the flexible electrode and the cerebral cortex will cause the electrode to mechanically strain the tissue, increase the risk of neural tissue damage and chronic inflammation, glial scars, etc. For traditional semi-invasive electrodes made of metal electrodes such as platinum and silicone rubber substrates, due to mechanical properties, traditional semi-invasive electrodes often slide on the surface of the cortex when the patient moves, which is not conducive to the stable recording of EEG signals. At present, there is a lack of a new neural electrode structure that can simultaneously achieve high-quality detection of EEG signals and cause little damage to neural tissue during long-term implantation. In addition, for neural sensors based on one-dimensional semiconductor nanowires, their sensing performance can be significantly improved by regulating the piezoelectric effect, but there is currently no method to accurately apply piezoelectric deformation to devices implanted in the body to induce piezoelectric effect.

[0003] In 2019, Gao et al. proposed a flexible magnetic micro-invasive probe electrode remotely driven by a magnetic field, named "Magnetic actuation of flexible microelectrode arrays for neural activity recordings" Nano letters, 2019, 19 (11): 8032-8039. In this work, a single probe electrode can be remotely driven by magnetic force and connected to the biological system in vivo, realizing the recording of neural activity in the peripheral nerves and cerebral cortex of mice. In 2023, Liu et al. proposed an injectable electronic device based on magnetic actuation with stable recording, omnidirectional steering and precise navigation capabilities. It can be driven by a magnetic field and further perform minimally invasive three-dimensional interpenetration in the brain, realizing the selective and multi-channel neural activity recording of remote areas deep in the brain. However, the deformation state of the above two probe structure electrodes requires a stable magnetic field to be applied to maintain. Summary of the invention

[0004] The present invention aims to solve the deficiencies of the prior art and proposes an implantable neural electrode device that can be detached from the cerebral cortex by magnetically controlled telescopic contact. Based on the principle of a magnetically controlled deformable micro-robot, magnetic particles are mixed with an elastomer to construct a substrate for the neural electrode using a magnetically controlled deformable material. The neural electrode structure is a planar electrode that can be fixed under the dura mater. The deformation and bending arch driven by the magnetic field is an effective contact between the middle top electrode and the cerebral cortex. The deformed state can be fixed by a polyimide film and a rectangular groove after the magnetic field is removed, avoiding instability of the neural-electrode interface caused by changes in the magnetic field. After the EEG signal test is completed, the neural electrode can be bent in the opposite direction by applying a reverse magnetic field, the polyimide film is pulled out of the rectangular groove, and the neural electrode is restored to a planar structure by an elastic component.

[0005] To achieve the above-mentioned object, the present invention provides the following scheme: an implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex, comprising: a flexible substrate, a magneto-deformable substrate, a magneto-deformable film, an elastic component and an electrode;

[0006] A plurality of neatly arranged rectangular grooves are provided on one side of the flexible substrate;

[0007] Two magneto-deformable films are respectively attached to two sides of the magneto-deformable substrate, and the magneto-deformable film on one side is used to fix the magneto-deformable substrate in the rectangular groove of the flexible substrate;

[0008] The electrodes are fixed on the magneto-deformable substrate and are used to collect brain electrical signals;

[0009] The elastic component is used to pull the deformed magneto-deformable substrate to restore the plane state.

[0010] Further preferably, the flexible substrate is made of PDMS material and has a thickness of 0.6 mm.

[0011] Further preferably, the magnetostrictive substrate is made of a polyimide film with a thickness of 0.025 mm.

[0012] Further preferably, the method for manufacturing the magnetostrictive film comprises:

[0013] After 400# NdFeB magnetic particles were mixed with PDMS liquid in a mass ratio of 1:1, the mixture was poured into a mold and placed in a 60°C oven for drying. A strong magnetic field of 1T was applied for magnetization to prepare the magneto-deformable film that was deformed by magnetic field drive.

[0014] Further preferably, the elastic component is cut into an S-shape by a laser cutting machine from a 0.5 mm thick polyimide film.

[0015] Further preferably, the electrode is a magnetically controlled neural electrode or a magnetically controlled piezoelectric zinc oxide nanowire sensor.

[0016] Further preferably, the driving method of the neural electrode device includes:

[0017] In the absence of a magnetic field, the neural electrode device is in a planar state; a magnetic field perpendicular to the plane direction is applied to the neural electrode device, and the magnetic field strength is gradually increased. As the magnetic field strength increases, the magneto-deformable substrate gradually bends, and the magneto-deformable film on one side of the rectangular groove is inserted into the rectangular groove of the flexible substrate at 60 mT; the magnetic field strength is continued to increase, and when the magnetic field strength reaches 120 mT, the magneto-deformable film is inserted into the right rectangular groove of the flexible substrate;

[0018] When a reverse 120 mT magnetic field is applied, the magneto-deformable substrate bends in the reverse direction, and the magneto-deformable film is separated from the rectangular groove of the flexible substrate; after the reverse magnetic field disappears, the neural electrode device returns to a planar state under the traction of the elastic component.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The device of the present invention is fixed under the dura mater and can bend under the drive of a magnetic field, thereby achieving effective contact between the neural electrode and the cerebral cortex. Compared with traditional semi-invasive neural electrodes, the detection quality and stability of EEG signals are improved. At the same time, the bent state can induce piezoelectric deformation, which can effectively enhance the sensitivity of neurobiosensors based on piezoelectric semiconductor nanowires in detecting neurotransmitters and neural electrical signals. Reverse loading of the magnetic field to cause the neural electrode to detach from the brain tissue and retract into the cerebral cortex can allow the neural electrode to contact the cerebral cortex only when testing is required, thereby avoiding long-term contact and friction between the long-term implanted flexible neural electrode and the cerebral cortex. This structure can induce a change in the state of the neural electrode by briefly applying a magnetic field, thereby avoiding the negative impact of long-term loading of a strong magnetic field to maintain deformation on humans. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the technical solution of the present invention, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0022] Figure 1 This is a schematic diagram of the structure of an implantable neural electrode device according to an embodiment of the present invention;

[0023] Among them, (a) is a plan view; (b) is a hierarchical structure diagram; (c) is a schematic diagram of the prepared magneto-deformable electrode; (d) is a schematic diagram of the prepared magneto-deformable zinc oxide nanowire neural biosensor;

[0024] Figure 2 This is a schematic diagram of the magnetization process of an embodiment of the present invention;

[0025] Among them, (a) is a schematic diagram of the magnetization principle; (b) is a schematic diagram of the magnetostrictive film when there is no magnetic field; (c) is a schematic diagram of the bending of the magnetostrictive film when a magnetic field is applied; (d) is a schematic diagram of the bending of the magnetostrictive film when a reverse magnetic field is applied;

[0026] Figure 3 Schematic diagram of a magnetically controlled neural electrode in different magnetic driving states according to an embodiment of the present invention;

[0027] Figure 4 This is a schematic diagram of the magnetic driving of the magnetically controlled piezoelectric zinc oxide nanowire sensor according to an embodiment of the present invention;

[0028] Among them, (a) is a schematic diagram of different magnetic driving states; (b) is a schematic diagram of the energy band change of the zinc oxide nanowire sensor under compressive strain and tensile strain caused by magnetic fields in opposite directions; (c) is a schematic diagram of the IV curve of the zinc oxide nanowire sensor in different states; (d) is a schematic diagram of the Schottky barrier change of the zinc oxide nanowire sensor in different states;

[0029] Figure 5 A schematic diagram of controllable contact / detachment between a magnetically driven neural electrode and cerebral cortical tissue according to an embodiment of the present invention;

[0030] Figure 6 This is a schematic diagram of the performance of the zinc oxide nanowire sensor detecting the dopamine sensor according to an embodiment of the present invention;

[0031] Among them, (a) is a schematic diagram of the piezoelectric effect enhancing the performance of zinc oxide nanowire sensors in detecting dopamine; (b) is a schematic diagram of the IV curve of the zinc oxide nanowire sensor at the initial dopamine concentration; (c) is a schematic diagram of the IV curve of the zinc oxide nanowire sensor at a tensile strain of 0.24% dopamine concentration; (d) is a schematic diagram of the IV curve of the zinc oxide nanowire sensor at a tensile strain of 0.36% dopamine concentration;

[0032] Figure 7 This is a schematic diagram of the performance of the zinc oxide nanowire sensor in detecting neural electrical signals according to an embodiment of the present invention;

[0033] Among them, (a) is a schematic diagram of the piezoelectric effect enhancing the performance of zinc oxide nanowire sensors in detecting neural electrical signals; (b) is a schematic diagram of the IV curve of zinc oxide nanowire sensors under different tensile strains; (c) is a schematic diagram of the current response obtained by stimulating the bullfrog sciatic nerve with different voltage pulses (0.2V, 0.4V) and measuring neural electrical pulses with zinc oxide nanowire sensors under different tensile strains;

[0034] Figure 8 This is a schematic diagram of the state transition of the magnetically controlled neural electrode / sensor driven by a magnet under the attenuation effect of 2 cm thick pork in an embodiment of the present invention. DETAILED DESCRIPTION

[0035] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0036] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0037] Embodiment 1:

[0038] like Figure 1 , which is a schematic diagram of the structure of an implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex proposed in this embodiment, comprising: a flexible substrate, a magneto-deformable substrate, a magneto-deformable film, an elastic component and an electrode.

[0039] Specifically, the plan view of the neural electrode device is as follows: Figure 1 (a) Figure 1 (b) is a schematic diagram of the hierarchical structure, in which a number of neatly arranged rectangular grooves are provided on one side of the flexible substrate, which is made of PDMS material with a thickness of 0.6 mm. The electrode is fixed on the magneto-deformable substrate for collecting EEG signals; the magneto-deformable substrate is made of polyimide film with a thickness of 0.025 mm. Two magneto-deformable films are attached to the magneto-deformable substrate, each with a thickness of 0.5 mm; wherein the magneto-deformable film on one side of the rectangular groove can be inserted into the rectangular groove to fix the deformation induced by the magnetic field. The elastic component uses a laser cutting machine to cut the 0.5 mm thick polyimide film into an S shape, which is used to pull the deformed magneto-deformable substrate back to a planar state. All parts are realized by solidifying PDMS liquid. The electrode in this embodiment can use a magnetically controlled neural electrode or a magnetically controlled piezoelectric zinc oxide nanowire sensor. Figure 1 (c) is a schematic diagram of the prepared magnetostrictive electrode. Figure 1 (d) Schematic diagram of the prepared magneto-deformable zinc oxide nanowire neural biosensor.

[0040] In this embodiment, the method for manufacturing the magneto-deformable film includes:

[0041] Based on the existing principle of magneto-deformable film, 400# NdFeB magnetic particles were mixed with PDMS liquid in a mass ratio of 1:1, poured into a mold and dried in a 60°C oven, and magnetized with a strong magnetic field of 1T to prepare a magneto-deformable film that was deformed by a magnetic field. The magnetization process and principle are as follows Figure 2 (a) shows that the magnetostrictive film in the absence of a magnetic field is Figure 2 (b) shows the bending of the magnetized film in different directions and magnetic fields. Figure 2 (c) and Figure 2 (d) as shown.

[0042] Embodiment 2:

[0043] In this embodiment, Figure 3 As shown, the driving method of the neural electrode device includes:

[0044] In the absence of a magnetic field, the neural electrode device is in a planar state (initial state, i.e., state ①); a magnetic field perpendicular to the plane direction is applied to the neural electrode device, and the magnetic field strength is gradually increased. As the magnetic field strength increases, the magneto-deformable substrate gradually bends, and the magneto-deformable film on one side of the rectangular groove is inserted into the rectangular groove of the flexible substrate at 60mT. At this time, the magneto-deformable substrate is in state ②-slightly bent; it is worth noting that after the magnetic field is withdrawn at this time, state ② can still be maintained. The magnetic field strength continues to increase. When the magnetic field strength reaches 120mT, the magneto-deformable film is inserted into the rectangular groove on the right side of the flexible substrate; at this time, the magneto-deformable substrate is in state ③-obviously bent.

[0045] When it is necessary to convert to a planar state, a reverse magnetic field of 120mT can be applied to the neural electrode device in state ③, and the magnetodeformable substrate bends in the opposite direction - state ④, and the magnetodeformable film detaches from the rectangular groove of the flexible substrate; after the reverse magnetic field disappears, the magnetodeformable substrate returns to a planar state under the traction of the elastic component.

[0046] Among them, the photos of magneto-deformable zinc oxide nanowire neural biosensors in different magnetic driving states are shown in Figure 2. Figure 4 (a) shown. Figure 4(b) shows the energy band changes of the zinc oxide nanowire sensor under compressive strain and tensile strain caused by magnetic fields in opposite directions. The prepared zinc oxide nanowire-based sensor is a top electrode mode, and the contact area formed by the silver paste electrode and the two ends of the zinc oxide nanowire is marked with a red dot. When compressive strain and tensile strain are applied, the piezoelectric potential formed in the electrical contact area is negative and positive, respectively, and the Schottky barriers at both ends of the zinc oxide nanowire sensor increase and decrease, respectively. Therefore, compared with state ①, the tensile piezoelectric deformation induced by the magnetic field in states ② and ③ gradually increases, Figure 4 (c) shows that the IV curve of the ZnO nanowire sensor is on an upward trend. Figure 4 (c) The calculated Schottky barriers at both ends gradually decrease. This phenomenon realizes the effective regulation of the Schottky barrier and helps to improve its sensing performance.

[0047] Embodiment three:

[0048] This embodiment illustrates the controllable contact / detachment between the magnetically driven neural electrode and the cerebral cortical tissue through experiments.

[0049] The magnetically controlled neural electrode was fixed on the top of the head of the SD rat. When the magnetically controlled neural electrode was in a flat state, the metal electrode did not contact the exposed cerebral cortex of the anesthetized rat. Figure 5 As shown in the upper left figure, only the noise signal is obtained, such as Figure 5 As shown in the upper right part of the figure. When the magnetically controlled neural electrode is driven by a temporarily applied magnetic field to transform into a bent state, the metal electrode is in full contact with the exposed cerebral cortex, as shown in the figure below. Figure 5 As shown in the figure in the lower left part, the electrophysiological signals of the anesthetized rat brain can be recorded by magnetically controlled neural electrodes, such as Figure 5 The lower right part of the figure is shown.

[0050] Embodiment 4:

[0051] like Figure 6 As shown in (a), the piezoelectric effect induced by a magnetic field can enhance the sensitivity of the magnetically controlled piezoelectric zinc oxide nanowire sensor in detecting dopamine (DA) molecules. Figure 6 As shown in (b), the IV curves corresponding to 0M and 100nM are almost overlapped, and the IV curve corresponding to 10μM is reduced to the limit, and the output current is close to zero in the range of (-1V to 1V). From this IV curve, it can be seen that the lowest and highest DA concentrations that the sensor can detect are higher than 100nM and lower than 10μM, respectively. When the tensile strain increases from 0.00 to 0.24% and 0.36%, the IV curves corresponding to 0M and 100nM are separated, and the IV curve corresponding to 10μM still has room to decline. The results show that the detection range of DA is greater than 100nM to 10μM, and the detection range can be expanded by the piezoelectric effect, such as Figure 6 (c) and Figure 6 (d) as shown.

[0052] Embodiment five:

[0053] like Figure 7 As shown in (a), the piezoelectric effect induced by a magnetic field can improve the performance of piezoelectric zinc oxide nanowire sensors in detecting neural electrical signals. When the stimulation voltage is 0.2V, a violent contraction of the frog peroneus muscle can be observed, that is, the action potential is generated and flows through the zinc oxide nanowire, but in the absence of external strain and when the tensile strain is 0.124%, the zinc oxide nanowire biosensor does not detect the weak characteristic signal of the action potential. When the tensile strain reaches 0.248%, the amplitude of the characteristic signal is about 0.08nA, and as the tensile strain increases, the amplitude of the characteristic signal increases to 0.35nA. The piezoelectric effect caused by tensile strain improves the detection ability of zinc oxide nanowire biosensors for weak neural electrical signals. Figure 7 (b) IV curves of ZnO nanowire sensors under different tensile strain levels; Figure 7 (c) The current response obtained by measuring nerve electrical pulses using a zinc oxide nanowire sensor when stimulating the bullfrog sciatic nerve with different voltage pulses (0.2V, 0.4V) and under different tensile strains.

[0054] Embodiment six:

[0055] Given that magnetically controlled neural electrodes / sensors are designed to achieve high-sensitivity detection in vivo, it is of great significance to remotely or even transcranially control implantable magnetically controlled neural electrodes / sensors through magnetic fields. If the magnetically controlled neural electrodes / sensors are implanted under the human skull, the magnetic field needs to penetrate the scalp, skull, intracranial cavity and arachnoid membrane. It is known that the magnetic field will not be attenuated or distorted by biological fluids and tissues. The key issue is that the intermediate frequency attenuates with distance. The thickness of the scalp and skull is between 2mm~3mm and 1cm~1.5cm, respectively. In this work, the MCPD is converted between a planar state and a bent state by the MF attenuated by a 2cm thick pigskin generated by a permanent magnet with a size of 100mm*50mm*20mm, as shown in FIG. Figure 8 As shown. Assuming that the magnetically controlled neural electrode / sensor is implanted and attached under the dura mater and arachnoid mater, the distance between the arachnoid mater and the pia mater of a person is about 0.5 cm. The stable bending state induced by the magnetic field of the magnetically controlled neural electrode / sensor can not only apply external strain to the piezoelectric biosensor, induce piezoelectric effect, and improve the sensing performance, but also realize a high-quality biological interface between the neural electrode and the brain tissue, and realize high-quality electrophysiological signal recording.

[0056] The embodiments described above are only descriptions of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A magnetically controlled telescopic contact-detachable implantable neural electrode device for cerebral cortex, characterized in that: include: Flexible substrate, magneto-deformable substrate, magneto-deformable film, elastic component and electrode; A plurality of neatly arranged rectangular grooves are provided on one side of the flexible substrate; Two magneto-deformable films are respectively attached to two sides of the magneto-deformable substrate, and the magneto-deformable film on one side is used to fix the magneto-deformable substrate in the rectangular groove of the flexible substrate; The electrodes are fixed on the magneto-deformable substrate and are used to collect brain electrical signals; The elastic component is used to pull the deformed magneto-deformable substrate to restore the plane state.

2. According to claim 1, the implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex is characterized in that: The flexible substrate is made of PDMS material and has a thickness of 0.6 mm.

3. According to claim 1, the implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex is characterized in that: The magnetostrictive substrate is a polyimide film with a thickness of 0.025 mm.

4. According to claim 1, the implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex is characterized in that: The method for manufacturing the magnetostrictive film comprises: After 400# NdFeB magnetic particles were mixed with PDMS liquid in a mass ratio of 1:1, the mixture was poured into a mold and placed in a 60°C oven for drying. A strong magnetic field of 1T was applied for magnetization to prepare the magneto-deformable film that was deformed by magnetic field drive.

5. According to claim 1, the implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex is characterized in that: The elastic component is cut into an S-shape by a laser cutting machine from a 0.5 mm thick polyimide film.

6. The implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex according to claim 1, characterized in that: The electrode is a magnetically controlled neural electrode or a magnetically controlled piezoelectric zinc oxide nanowire sensor.

7. The implantable neural electrode device for magnetically controlled telescopic contact detachment from the cerebral cortex according to claim 1, characterized in that: The driving method of the neural electrode device comprises: In the absence of a magnetic field, the neural electrode device is in a planar state; a magnetic field perpendicular to the plane direction is applied to the neural electrode device, and the magnetic field strength is gradually increased. As the magnetic field strength increases, the magneto-deformable substrate gradually bends, and the magneto-deformable film on one side of the rectangular groove is inserted into the rectangular groove of the flexible substrate at 60 mT; the magnetic field strength is continued to increase, and when the magnetic field strength reaches 120 mT, the magneto-deformable film is inserted into the right rectangular groove of the flexible substrate; When a reverse 120 mT magnetic field is applied, the magneto-deformable substrate bends in the reverse direction, and the magneto-deformable film is separated from the rectangular groove of the flexible substrate; after the reverse magnetic field disappears, the neural electrode device returns to a planar state under the traction of the elastic component.

Images